Pilot Comparison of Standard Antiviral Therapy With and Without 12 Weeks of Betaine in Genotype 1 Naive Patients
The primary purpose of the study is to compare the safety and effectiveness of standard treatment for chronic hepatitis C using peginterferon alpha-2a (Pegasys) and ribavirin (Copegus) to those same medications plus a dietary supplement called betaine when added for the first 12 weeks of treatment.
Peginterferon alpha-2a (Pegasys) and ribavirin (Copegus) are approved by the FDA (Food and Drug Administration) for the treatment of chronic hepatitis C.
Betaine is a dietary supplement and occurs naturally in the body. It is not a medication regulated by the FDA or an approved drug for chronic hepatitis C.
|Chronic Hepatitis C||Drug: Peginterferon alpha-2a and ribavirin Drug: Peginterferon alpha-2a , ribavirin and betaine|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Comparison of Standard Therapy,Peginterferon Alpha-2a + Ribavirin for 48 Weeks VS Peginterferon Alph-2a + Ribavirin + Betaine for 12 Weeks Followed by 36 Weeks Standard Therapy in Untreated Adults With Chronic Hepatitis C Genotype 1|
- Sustained Viral Response 24 weeks following the end of anti-viral therapy [ Time Frame: 72 weeks ]
- Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy [ Time Frame: 12 weeks ]
- Comparison of the safety of the two treatment regimens [ Time Frame: 48 weeks ]
- Comparison of ALT normalization between the two regimens [ Time Frame: 48 weeks ]
- Comparison of the effect on interferon gene signaling in peripheral blood mononuclear cells between the two regimens in the first 12 weeks of therapy. [ Time Frame: 12 weeks ]
|Study Start Date:||April 2008|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Peginterferon alpha-2a q week plus weight based ribavirin (800-1400mg/day)in 2 divided daily doses
Drug: Peginterferon alpha-2a and ribavirin
Peginterferon alpha-2a 180mcg by subcutaneous injection every week and weight based ribavirin, 800 to 1400mg/day by mouth in two divided doses every day for 48 weeks
Active Comparator: 2
Peginterferon alpha-2a q week plus weight based ribavirin (800-1400mg/day) in 2 divided daily doses plus betaine (20gm/day) in 2 divided doses for 12 weeks followed by Peginterferon alpha-2a q week plus weight based ribavirin (800-1400mg/day) in 2 divided daily doses for 36 weeks
Drug: Peginterferon alpha-2a , ribavirin and betaine
Peginterferon alpha-2a 180mcg given by subcutaneous injection every week plus weight based ribavirin 800 to 1400 mg/day by mouth in divided doses twice a day plus betaine 10 gm dissolved in juice twice a day for twelve weeks followed by peginterferon alpha-2a 180 mcg given by subcutaneous injection every week plus weight based ribavirin 800 to 1400mg/day by mouth in divided doses twice a day for 36 weeks.
Although pegylated alpha interferon and ribavirin will likely be part of the core therapy for chronic HCV for the next several years, there are a number of complimentary antiviral agents in development including protease or polymerase inhibitors, RNA vaccines and immunomodulators (5). However, it would be unlikely to have FDA approval for any of these newer agents before the next 3 - 5 years, i.e. 2010-2012.
Betaine, a naturally occurring anti-oxidant metabolite of choline and an amino acid analog (tri-methyl-glycine), serves as a methylation agent to re-methylate damaged cell proteins or enzymes (6). By virtue of its metabolic role in decreasing toxic metabolites, betaine also protects against alcohol-induced fatty liver and apoptosis. Recently, pilot studies performed both at the Mayo Clinic and here at UNMC showed its applicability as a treatment of non-alcoholic fatty liver in human subjects (7, 8).
Betaine has also recently been found to promote interferon function by overcoming HCV - induced inhibition of interferon signaling (9). Naturally-occurring HCV proteins during human infection can hypo-methylate proteins integral to the Jak - STAT (signal transducers and activators of transcription) pathway, thereby inhibiting the antiviral activity of interferon. In cultured cells betaine administration, in a physiologically attainable concentration, restored STAT methylation and improved interferon signaling (9).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00571714
|United States, Nebraska|
|Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198|
|Principal Investigator:||Mark E Mailliard, M.D.||University of Nebraska|